Persistent respiratory tract colonization of preterm infants with the genital mycoplasma, Ureaplasma urealyticum, is a significant risk factor for the development of the chronic lung disorder Bronchopulmonary Dysplasia (BPD). Trials of antibiotic therapy with erythromycin in the first few weeks of life failed to eradicate respiratory tract colonization and the development of BPD in Ureaplasma- colonized infants. There are no current effective therapies for the treatment of Ureaplasma in preterm infants. Our long-term objective is to develop therapies to eradicate Ureaplasma from the respiratory tract of preterm infants and prevent or ameliorate Ureaplasma-mediated lung injury. The new 14-membered macrolides and the related 15-member azalides have immunomodulatory effects, including effects on neutrophil function and inhibition of inflammatory cytokine release in vitro (1). The azalide azithromcyin has properties that make it an ideal candidate for therapy to prevent Ureaplasma-mediated lung injury in preterm infants. Azithromycin 1) inhibits neutrophil influx and chemoattractant release in murine lung injury models (2);2) exhibits higher potency than erythromycin against clinical Ureaplasma isolates in vitro (3-5);and 3) is preferentially concentrated in alveolar epithelial lining fluid and macrophages (6, 7). We hypothesize that intravenous azithromycin therapy will prevent BPD in Ureaplasma-infected preterm infants by accelerating pathogen clearance and/or down-regulating the pulmonary inflammatory response. Currently, the pharmacokinetics, safety, and biologic effects of azithromycin in the preterm population are unknown. The specific aims of this exploratory pilot proposal will address the first steps preparatory to Phase III safety and efficacy trials of azithromycin in the preterm population. The current proposal will be a Phase 1 non-randomized, open-label, single-dose, pharmacokinetic (PK) study. The specific aims are: 1) to characterize and compare the single dose pharmacokinetics (PK), safety and tolerability, and biologic effects of 10 mg/kg and 20 mg/kg intravenous azithromcyin in mechanically ventilated preterm neonates born 24-28 weeks gestation who are at high-risk for Ureaplasma respiratory tract colonization and the development of BPD;and 2) to prepare for planned Phase III efficacy trials by evaluating the effectiveness of a central laboratory for identification of Ureaplasma-positive infants. At the completion of this study, we anticipate that we will have determined the single dose PK of azithromycin and assessed the drug's safety profile in preterm infants at risk for Ureaplasma colonization and BPD. In addition, we will have established the optimal methods to document Ureaplasma colonization and eradication. These data will directly lead to future multi-dose pharmacokinetic/pharmacodynamic studies and randomized safety and efficacy trials of azithromycin to counteract the detrimental effects of Ureaplasma in the preterm lung. Babies who are born prematurely with an infection with the bacteria Ureaplasma may develop a chronic lung disease called Bronchopulmonary Dysplasia (BPD). Currently, there are no effective therapies to treat this infection or prevent the complication BPD in infected infants. This study will evaluate the safety and pharmacokinetics (how the body processes the drug) of the antibiotic azithromycin in preterm babies at risk for the Ureaplasma infection and the complication BPD.